Prostate cancer is the most common malignancy among men in the United States and also ranks as the second most common cause of cancer death in males. The prostate specific antigen (PSA) blood test, in addition to the digital rectal exam, have traditionally been the preferred modalities to screen for prostate cancer. While prostate cancer screening leads to an early diagnosis of prostate cancer, which in turn permits curative treatment, it also has significant limitations because serum PSA is not specific to prostate cancer. One of the major limitations of PSA screening is that serum PSA can be elevated in patients with other common benign conditions, such as benign prostatic hyperplasia, prostatitis, or after minor clinical procedures, such as transrectal ultrasound. Accordingly, for every four men that have prostate biopsies, one case of prostate cancer is detected.
PSA is also not a reliable biomarker for aggressive prostate cancer. High grade prostate cancers may actually produce less PSA and the absolute PSA number does not accurately reflect the aggressiveness of disease. For men diagnosed with prostate cancer many have clinically insignificant disease, which will never become symptomatic in their lifetime. This “over-diagnosis” of clinically insignificant prostate cancer from PSA screening has been estimated to be as high as 30% with subsequent over-treatment. The side effects of prostate cancer treatment may include unnecessary painful biopsies, surgical complications, radiation burns, incontinence, erectile dysfunction, bowel injury, and patient anxiety. Thus, there is a clear need for an improved biomarker for prostate cancer.
Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in peroxisomal beta-oxidation of dietary branched-chained fatty acids. AMACR has been consistently overexpressed in prostate cancer epithelium; hence it becomes an ideal specific biomarker for cancer cells within the prostate gland. Over-expression of AMACR may increase the risk of prostate cancer, because its expression is increased in premalignant lesions (prostatic intraepithelial neoplasia). Furthermore, epidemiologic, genetic and laboratory studies have pointed to the importance of AMACR in prostate cancer. Genome-wide scans of linkage in hereditary prostate cancer families have demonstrated that the chromosomal region for AMACR (5p 13) is the location of a prostate cancer susceptibility gene and AMACR gene sequence variants (polymorphisms) have been shown to co-segregate with cancer of the prostate in families with hereditary prostate cancer.